Abstract
Oncolytic virotherapy is a promising cancer treatment that harnesses the power of viruses. Through genetic engineering, these viruses are cultivated to infect and destroy cancer cells. While this therapy has shown success in a range of clinical trials, an open problem in the field is to determine more effective perturbations of these viruses. In this work, we use a controlled therapy approach to determine the optimal treatment protocol for a delayed infection from an immune-evading, coated virus. We derive a system of partial differential equations to model the interaction between a growing tumour and this coated oncolytic virus. Using this system, we show that viruses with inhibited viral clearance and infectivity are more effective than uncoated viruses. We then consider a hierarchical level of coating that degrades over time and determine a nontrivial initial distribution of coating levels needed to produce the lowest tumour volume. Interestingly, we find that a bimodal mixture of thickly coated and thinly coated virus is necessary to achieve a minimum tumour size. Throughout this article we also consider the effects of immune clearance of the virus. We show how different immune responses instigate significantly different treatment outcomes.
Highlights
Oncolytic viruses are genetically engineered viruses that preferentially target and destroy cancer cells [1]
To investigate the applicability of this suggested treatment improvement and to optimise the protocol, we have developed a system of Partial differential equations (PDEs) based on their model, that incorporates the interaction between an oncolytic virus and a population of tumour cells
Extending both of the modelling frameworks in [30] and [15], we developed a system of PDEs that considered the spatial interaction of an oncolytic virus with a growing population of susceptible tumour cells
Summary
Oncolytic viruses are genetically engineered viruses that preferentially target and destroy cancer cells [1]. Nanoparticles have been investigated as a viral DNA and RNA delivery system as they can be engineered to have a decreased immune response [12], and their physical properties can be used to provide controlled viral release and diminish infectivity, maintaining an elevated local concentration [4, 13, 14]. Polymerbased nanomaterials, such as polyethyleneglycol (PEG), have been shown to be effective at shielding particles from the extracellular environment and preventing clearance [12]
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